Clinical Scenario

A 42-year-old woman presents with a longstanding history of low back pain. Her pain has not improved with over-the-counter analgesics or physical therapy, and she is requesting a new pain medication. Treating her with an antidepressant is a consideration, but the benefits are uncertain.

Clinical Question

Are medications such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and atypical antidepressants effective for the treatment of nonspecific low back pain?

Evidence-Based Answer

Although antidepressants have been shown to be superior to placebo in some forms of chronic pain, they do not reduce pain or improve functional status or depression in patients with nonspecific low back pain.

Practice Pointers

Antidepressants are prescribed for a variety of chronic pain syndromes. Nearly one fourth of primary care physicians in the United States prescribe antidepressants for low back pain.1 There is some evidence to support this practice.2–4 The logic behind prescribing antidepressants for various pain syndromes is threefold: first, patients with chronic pain frequently have comorbid depression, and treating depression may increase pain tolerance; second, many antidepressants are thought to have an analgesic effect separate from their mood-elevating benefit; and third, the sedating effects of many of these medications are thought to improve insomnia in patients with low back pain. However, according to this Cochrane review, current evidence does not support the treatment of low back pain with antidepressants.

The authors of this study found 10 randomized controlled trials published between 1976 and 2005 that compared various anti-depressant medications with placebo. Studies included a variety of antidepressant medications, including TCAs, SSRIs, and atypical antidepressants. Outcome measures varied and included decreased pain intensity, improved functional status, and improved mood. However, there was inconsistency between the trials with respect to patient selection (pain duration), antidepressant dose, treatment duration, and number of patients with depression. Six of the 10 studies were considered high-quality. The authors estimate that there are sufficient high-quality data to conclude that the evidence does not support the use of antidepressants to reduce pain or depression in patients with low back pain. This review does not apply to patients who have major depression or other pain syndromes (e.g., neuropathic pain, fibromyalgia).

Although this review concluded that antidepressants are not effective for the treatment of low back pain, other recent systematic reviews that used slightly different methods came to divergent conclusions. The Cochrane review included all antidepressants and all patients with low back pain (including acute and chronic), and patients with and without associated radiculopathy, herniated disc, and spondylolisthesis. It excluded back pain from a specific cause, such as infection, metastasis, or rheumatoid arthritis. It is possible that specific antidepressants might be effective for subgroups of patients with low back pain. The American College of Physicians and the American Pain Society recently published a joint practice guideline based on their own systematic review.5 This guideline recommends TCAs, but not SSRIs, for chronic low back pain.6 Additionally, the review addressed adverse effects of antidepressants. Not unexpectedly, this was a significant issue because the antidepressants studied were associated with a higher rate of dry mouth, constipation, drowsiness, and dizziness than placebo.

Cochrane Abstract

Background: Antidepressants are commonly used in the management of low back pain. However, their use is controversial.

Objectives: The aim of this review was to determine whether antidepressants are more effective than placebo for the treatment of nonspecific low back pain.

Selection Criteria: The authors included randomized controlled trials that compared antidepressant medication with placebo for patients with nonspecific low back pain, and used at least one clinically relevant outcome measure.

Data Collection and Analysis: Two blinded review authors independently extracted data and assessed the methodological quality of the trials. Meta-analyses were used to examine the effect of antidepressants on pain, depression, and function, and the effect of antidepressant type on pain. To account for studies that could not be pooled, additional qualitative analyses were performed using the levels of evidence recommended by the Cochrane Back Review Group.

Main Results: Ten trials that compared antidepressants with placebo were included in this review. The pooled analyses showed no difference in pain relief (six trials; standardized mean difference [SMD] = −0.06; 95% confidence interval [CI], −0.28 to 0.16) or depression (two trials; SMD = 0.06; 95% CI, −0.29 to 0.40) between antidepressant and placebo treatments. The qualitative analyses found conflicting evidence on the effect of antidepressants on pain intensity in chronic low back pain, and no clear evidence that antidepressants reduce depression in patients with chronic low back pain. Two pooled analyses showed no difference in pain relief between different types of antidepressants and placebo. The authors' findings were not altered by the sensitivity analyses, which varied the level of methodological quality required for inclusion in the meta-analyses to allow data from additional trials to be examined. Two additional trials were identified in September 2007 and await assessment.

Authors' Conclusions: There is no clear evidence that antidepressants are more effective than placebo in the management of patients with chronic low back pain. These findings do not imply that severely depressed patients with back pain should not be treated with antidepressants; furthermore, there is evidence for their use in other forms of chronic pain.

These summaries have been derived from Cochrane reviews published in the Cochrane Database of SystematicReviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the originalreviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minorediting changes have been made to the text (http://www.cochrane.org).

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6. Chou R,
Qaseem A,
Snow V,
et al.,
for the Clinical Efficacy Assessment Subcommittee.
Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society [published correction appears in Ann Intern Med. 2008;148(3):247–248]. Ann Intern Med.
2007;147(7):478–491,I45.

The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Dr. Kassis presents a clinical scenario and question based on the Cochrane Abstract, followed by an evidence-based answer and a critique of the review. The practice recommendations in this activity are available at http://www.cochrane.org/reviews/en/ab001703.html.

The series coordinator for AFP is Clarissa Kripke, MD, Department of Family and Community Medicine, University of California, San Francisco.